Self-delivering Nanoemulsions for Dual Fluorine-19 MRI and Fluorescence Detection

Abstract

We report the design, synthesis, and biological testing of highly stable, nontoxic perfluoropolyether (PFPE) nanoemulsions for dual 19F MRI-fluorescence detection. A linear PFPE polymer was covalently conjugated to common fluorescent dyes (FITC, Alexa647 and BODIPy-TR), mixed with pluronic F68 and linear polyethyleneimine (PEI), and emulsified by microfluidization. Prepared nanoemulsions (<200 nm) were readily taken up by both phagocytic and non-phagocytic cells in vitro after a short (approximately 3 h) co-incubation. Following cell administration in vivo, 19F MRI selectively visualizes cell migration. Exemplary in vivo MRI images are presented of T cells labeled with a dual-mode nanoemulsion in a BALB/c mouse. Fluorescence detection enables fluorescent microscopy and FACS analysis of labeled cells, as demonstrated in several immune cell types including Jurkat cells, primary T cells and dendritic cells. The intracellular fluorescence signal is directly proportional to the 19F NMR signal and can be used to calibrate cell loading in vitro.

Fluorinated and Charged Hydrogenated Alkanethiolates Grafted on Gold: Expanding the Diversity of Mixed-Monolayer Nanoparticles for Biological Applications

“…9 Fluorinated soft NPs have been, indeed, proposed as drug delivery systems for doxorubicin. 10,11 An additional feature of fluorinated materials, including AuNPs, is that they may be easily engineered into contrast agents for 19 F magnetic resonance imaging, 12,13 and by combining this application with drug delivery, novel theranostic platforms may become available. 11 As far as monolayer protected AuNPs are concerned, the immiscibility of F-and H-thiolate ligands, arising from the lipophobicity of fluorocompounds, favors their self-sorting, with formation of domains, on the NPs surface.…”

Enhanced cellular uptake and long-term retention of chitosan-modified iron-oxide nanoparticles for MRI-based cell tracking

“…[15][16][17][18] Conveniently, macrophages phagocytose micronsized particles from their surroundings, and so labeling of these particular cells proved straightforward. Immortalized cell lines have been successfully labeled using synthetic transfection reagents, such as lipofectamine 19 and polyethylene imine (PEI); 20 however, such reagents are unacceptably cytotoxic at even low concentrations to a variety of primary somatic and stem cell types, limiting their utility for labeling of such cells. Surface conjugation of small molecules, such as cholera toxin B, and biologically active oligopeptides, such as arginineglycine-aspartic acid (RGD), to nanoparticles has also yielded high rates of endocytic cellular uptake; 21,22 however, trafficking through endo-lysosomal pathways beyond uptake causes these particles to be rapidly evacuated from cells.…”

Gold nanoparticles protected by fluorinated ligands: Syntheses, properties and applications

“…In this respect, it is important to stress that some fluorinated compounds such as the perfluoro alkanoic and perfluorosulfonic acids, indeed display non-negligible long term toxicity. Interesting building blocks in the design of the nanoparticles' monolayer are perfluoropolyethers, these compounds are being extensively studied as 19 F MRI tracers in vitro and in vivo [49][50][51] and the data support a limited toxicity. Given the low cytotoxicity of these systems, application for cell tracking in vivo could be foreseen in analogy to nanoemulsion containing perfluoropolyether (PFPE) described by Ahrens [52,53].…”